摘要
蛋白降解靶向嵌合体(proteolytic targeting chimera,PROTAC)是一种通过泛素-蛋白酶体系统选择性降解靶蛋白的新技术。PROTAC是一类异双功能分子,其中包含靶向目标蛋白质的配体,募集E3连接酶的配体和连接这2个配体的接头。与传统抑制剂相比,它们在功效、选择性和耐药性方面均具有许多优势。因此,近二十年来已经开发了许多有前途的PROTACs,尤其是小分子PROTACs。本文选择CRBN、VHL、MDM2和cIAP14种常见E3连接酶为代表,针对不同的靶向目标进行分类,在阐述4种E3连接酶各自特点的同时,也综述了基于不同E3连接酶的小分子PROTACs的研究进展。
Proteolytic-targeting chimera(PROTAC)is a new technology to selectively degrade target proteins via ubiquitin-proteasome system.PROTACs are a class of heterobifunctional molecules,which contain a ligand targeting the protein of interest,a ligand recruiting an E3 ligase and a linker connecting these two ligands.Comapred with traditional inhibitor,they provide several advantages in potency,selectivity and drug resistance.Thus,many promising PROTACs have been developed in the recent two decades,especially small-molecule PROTACs.This review selects 4 common E3 ligases,CRBN,VHL,MDM2 and cIAP1 as representatives,and classifies different target targets.It also summarizes the progress of small-molecule PROTACs based on different E3 ligases while describing the characteristics of these four E3 ligases.
作者
谢妙红
高明明
凌佳楠
杜文婷
XIE Miaohong;GAO Mingming;LING Jianan;DU Wenting(Hangzhou Medical College,Hangzhou 310053,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2021年第22期2891-2899,共9页
Chinese Journal of Modern Applied Pharmacy
基金
浙江省自然科学基金项目(LY21H300003)
国家级大学生创新创业训练计划项目(202113023007)。
